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Synaptic Messengers, Inflammatory Mediators, and Neuronal Plasticity in Cerebral Ischemia

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Maturation Phenomenon in Cerebral Ischemia II

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Summary

Cerebral ischemia activates the production of both endogenous and exogenous mediators of the inflammatory response. Using the middle cerebral artery occlusion suture model in the rat, we have found that occlusion followed by reperfusion leads to a remarkable induction of cyclo-oxygenase (COX) 2, both in the infarcted area and in the penumbra, occurring 6h after 2h of ischemia followed by 3h of reperfusion. COX-1, the constitutive enzyme, does not display changes under these conditions. Recent studies in our laboratory have also shown that in a kainic acid induced brain damage model COX-2 induction occurs at the transcriptional level, since nuclear runs on assays in isolated nuclei from the hippocampus as a function of time after injury matched the profile of changes in COX-2 mRNA abundance. Moreover, plateletactivating factor (PAF) is an activator of COX-2 transcription in transfected cells, and PAF antagonists in vivo block the injury-induced COX-2 expression. Therefore phospholipase A2 activation and PAF generation in cerebral ischemia link the formation of prostaglandins through COX-2 induction. These signaling pathways may be transneuronally controlled through excitatory amino acid neurotransmitters. It is hypothesized that phospholipase A2 activation, PAF accumulation, and COX-2 induction are reduced during the development of enhanced tolerance to ischemic injury.

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References

  1. Aveldaño MI, Bazan NG (1975) Rapid production of diacylglycerols enriched in 20:4 and stearate during early brain ischemia. J Neurochem 25: 919–920

    Article  PubMed  Google Scholar 

  2. Bazan HEP, Tao Y, Bazan NG (1993) Platelet-activating factor induces collagenase expression in corneal epithelial cells. Proc Natl Acad Sci USA 90: 8678–8682

    Article  PubMed  CAS  Google Scholar 

  3. Bazan NG (1970) Effects of ischemia and electroconvulsive shock on free fatty acid pool in the brain. Biochim Biophys Acta 218: 1–10

    PubMed  CAS  Google Scholar 

  4. Bazan NG, Fletcher BS, Herschman HR, Mukherjee PK (1994) Platelet-activating factor and retinoic acid synergistically activate the inducible prostaglandin synthase gene. Proc Natl Acad Sci USA 91: 5252–5256

    Article  PubMed  CAS  Google Scholar 

  5. Birkle DL, Bazan NG (1987) Effect of bicuculline-induced status epilepticus on prostaglandins and hydroxyeicosatetraenoic acids in rat brain subcellular fractions. J Neurochem 48: 1768–1778

    Article  PubMed  CAS  Google Scholar 

  6. Bonventre JV, Koroshetz WJ (1993) Phospholipase A2 (PLA2) activity in gerbil brain: characterization of cytosolic and membrane-associated forms and effects of ischemia and reperfusion on enzymatic activity. J Lipid Mediat 6: 457–471

    PubMed  CAS  Google Scholar 

  7. Dell’ Albani P, Condorelli DF, Mudo G, Amico C, Bindoni M, Belluardo N (1993) Platelet-activating factor and its methoxy analogue ET-18-OCH3 stimulate immediate-early gene expression in rat astroglial cultures. Neurochem Int: 22: 567–574

    Article  PubMed  Google Scholar 

  8. Doucet JP, Bazan NG (1993) Excitable membranes, lipid messengers and immediated-early genes. Alteration of signal transduction in neuromodulation and neurotrauma. Mol Neurobiol 6: 407–424

    Article  Google Scholar 

  9. Francescangeli E, Goracci G (1989) The de novo biosynthesis of platelet-activating factor in rat brain. Biochem Biophys Res Commun 161: 107–112

    Article  PubMed  CAS  Google Scholar 

  10. Futaki N, Takahashi S, Yokoyama M, Arai I, Higuchi S, Otomo S (1994) NS-398, a new anti-inflammatory agent, selectively inhibits prostaglandin G/H synthase/cyclooxygenase (COX-2) activity in vitro. Prostaglandins 47: 55–59

    Article  PubMed  CAS  Google Scholar 

  11. Gilboe DD, Kintner D, Fitzpatrick JH, Emoto SE, Esanu A, Braquet PG, Bazan NG (1991) Recovery of postischemic brain metabolism and function following treatment with a free radical scavenger and platelet activating factor. J Neurochem 56: 311–319

    Article  PubMed  CAS  Google Scholar 

  12. Goetzl EJ, An S, Smith WL (1995) Specificity of expression of eicosanoid mediators in normal physiology and human disease. FASEB J 9: 1051–1058

    PubMed  CAS  Google Scholar 

  13. Hallenbeck JM, Furlow TW (1979) Prostaglandin I2 and indomethacin prevent inhibition of postischemic brain reperfusion in the dog. Stroke 10: 629–637

    Article  PubMed  CAS  Google Scholar 

  14. Herschman HR (1994) Regulation of prostaglandin synthase-1 and prostaglandin synthase-2. Cancer Metastasis Rev 13: 241–256

    Article  PubMed  CAS  Google Scholar 

  15. Honda Z, Nakamura M, Miki I, Minami M, Wantabe T, Seyama Y, Okado H, Toh H, Ito K, Miyamoto T, Shimizu T (1991) Cloning by functional expression of platelet-activating factor receptor from guinea-pig lung. Nature 394: 342–346

    Article  Google Scholar 

  16. Kato K, Clark GD, Bazan NG, Zormuski CF (1994) Platelet-activating factor as a potential retrograde messenger in CAI hippocampal long-term potentiation. Nature 367: 179–182

    Article  Google Scholar 

  17. Kiessling M, Gass P (1993) Immediate early gene expression in experimental epilepsy. Brain Pathol 3: 381–393

    Article  PubMed  CAS  Google Scholar 

  18. Kogure K, Kato H (1993) Altered gene expression in cerebral ischemia. Stroke 24: 2121–2127

    Article  PubMed  CAS  Google Scholar 

  19. Kujubu DA, Fletcher BS, Varnum BC, Lim RW, Herschman HR (1991) TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. J Biol Chem 266: 12866–12872

    PubMed  CAS  Google Scholar 

  20. Kumar R, Harvey S, Kester N, Hanahan D, Olson M (1988) Production and effects of platelet-activating factor in the rat brain. Biochim Biophys Acta 963: 375–383

    PubMed  CAS  Google Scholar 

  21. Kunz D, Gerard NP, Gerard C (1992) The human leukocyte PAF receptor, cDNA cloning, cell surface expression and construction of a novel epitope-bearing analog. J Biol Chem 267: 9101–9106

    PubMed  CAS  Google Scholar 

  22. Marcheselli VL, Bazan NG (1994) Platelet-activating factor is a messenger in the electroconvulsive shock-induced transcriptional activation of c-fos and zif-268 in hippocampus. J Neurosci Res 37: 54–61

    Article  PubMed  CAS  Google Scholar 

  23. Marcheselli VL, Bazan NG (1996) Sustained induction of prostaglandin endoperoxide synthase-2 by seizures in hippocampus: inhibition by a platelet-activating factor antagonist. J Biol Chem 271: 24794–24799

    Article  PubMed  CAS  Google Scholar 

  24. Marcheselli VL, Rossowska M, Domingo MT, Braquet P, Bazan NG (1990) Distinct platelet-activating factor binding sites in synaptic endings and in intracellular membranes of rat cerebral cortex. J Biol Chem 265: 9140–9145

    PubMed  CAS  Google Scholar 

  25. Mazer B, Domenico J, Sawami H, Gelfand EW (1991) Platelet-activating factor induces an increase in intracellular calcium and expression of regularity genes in human B lymphoblastoma cells. J Immunol 146: 1914–1920

    PubMed  CAS  Google Scholar 

  26. Moises J, Allan G, Marcheselli VL, Mahandere V, Bazan NG (1994) A PAF antagonist inhibits the expression of hippocampal immediate early genes in a kindling model of epileptogenesis. Epilepsia 35: 139

    Google Scholar 

  27. Morita I, Schindler M, Regier MK, Otto JC, Hori T, DeWitt DL, Smith WL (1995) Different intracellular locations for prostaglandin endoperoxide H synthase-1 and -2. J Biol Chem 270: 10902–10908

    Article  PubMed  CAS  Google Scholar 

  28. O’Banion MK, Sadowski HB, Winn V, Young DA (1991) A serum- and glucocorticoidregulated 4-kilobase mRNA encodes a cyclooxygenase-related protein. J Biol Chem 266: 23261–23267

    PubMed  Google Scholar 

  29. Pan Z, Kravchenko VV, Ye RD (1995) Platelet activating factor stimulates transcription of the heparin-binding epidermal growth factor-like growth factor in monocytes. Correlation with an increased kappa B binding activity. J Biol Chem 270: 7787–7790

    Article  PubMed  CAS  Google Scholar 

  30. Panetta T, Marcheselli VL, Braquet P, Spinnewyn B, Bazan NG (1987) Effects of a platelet-activating factor antagonist (BN 52021) on free fatty acids, diacylglycerols, polyphosphoinositides and blood flow in the gerbil brain: inhibition of ischemia-reperfusion induced cerebral injury. Biochem Biophys Res Commun 149: 580–587

    Article  PubMed  CAS  Google Scholar 

  31. Prehn JHM, Krieglstein J (1993) Platelet-activating factor antagonists reduce excitotoxic damage in cultured neurons from embryonic chick telencephalon and protect the rat hippocampus and neocortex from ischemic injury in vivo. J Neurosci Res 34: 179–188

    Article  PubMed  CAS  Google Scholar 

  32. Prescott SM, Zimmerman GA, McIntyre TM (1990) Platelet-activating factor. J Biol Chem 265: 17381–17384

    PubMed  CAS  Google Scholar 

  33. Smith CS, Shearer WT (1994) Activation of NF-kappa B and immunoglobulin expression in response to platelet-activating factor in a human B cell line. Cell Immunol 155: 292–303

    Article  PubMed  CAS  Google Scholar 

  34. Squinto SP, Block AL, Braquet P, Bazan NG (1989) Platelet-activating factor stimulates a Fos/Jun/ AP-1 transcriptional signaling system in human neuroblastoma cells J Neurosci Res 24: 558–566

    Article  PubMed  CAS  Google Scholar 

  35. Sugimoto T, Tsuchimochi H, McGregor CG, Mutoh H, Shimizu T, Kurachi Y (1992) Molecular cloning and characterization of the platelet-activating factor receptor from human heart. Biochem Biophys Res Commun 189: 617–624

    Article  PubMed  CAS  Google Scholar 

  36. Tao Y, Bazan NG, Bazan HEP (1995) Platelet-activating factor (PAF) increases prostaglandin synthase-2 (COX-2) gene expression in corneal epithelium. Arvo Abstr 36: S573

    Google Scholar 

  37. Tripathi Y, Kandala J, Guntaka R, Lim R, Shukla S (1991) Platelet-activating factor induces expression of early response genes c-fos and TIS-1 in human epidermoid carcinoma-432 cells. Life Sci 49: 1761–1767

    Article  PubMed  CAS  Google Scholar 

  38. Yamagata K, Andreasson KI, Kaufmann WE, Barnes CA, Worley PF (1993) Expression of a mitogen-inducible cyclooxygenase in brain neurons: Regulation by synaptic activity and glucocorticoids. Neuron 11: 371–386

    Article  PubMed  CAS  Google Scholar 

  39. Yoshijara Y, Watanabe Y (1990) Translocation of phospholipase A2 from cytosol to membranes in rat brain induced by calcium ions. Biochem Biophys Res Commun 170: 484–490

    Article  Google Scholar 

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Authors and Affiliations

  1. LSU Eye Center and Neuroscience Center, Louisiana State University Medical Center School of Medicine, 2020 Gravier Street, Suite B, New Orleans, LA, 70112, USA

    N. G. Bazan

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  1. N. G. Bazan
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Editors and Affiliations

  1. Department of Neurosurgery, Musashino Red Cross Hospital, 1-26-1, Kyonan-cho, 180, Musashino-shi, Tokyo, Japan

    Umeo Ito

  2. Faculty of Medicine Department of Neurosurgery, University of Tokyo, 7-3-1, Hongo, 113, Bunkyo-ku, Tokyo, Japan

    Takaaki Kirino

  3. Department of Neuropathology Medical Research Institute, Tokyo Medical and Dental University, Yushima 1-5-45, 113, Bunkyo-ku, Tokyo, Japan

    Toshihiko Kuroiwa

  4. National Institutes of Health, Bethesda, MD, 20892-4128, USA

    Igor Klatzo (Former Chief of the Laboratory of Neuropathology and Neuroanatomical Sciences) (Former Chief of the Laboratory of Neuropathology and Neuroanatomical Sciences)

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© 1997 Springer-Verlag Berlin Heidelberg

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Bazan, N.G. (1997). Synaptic Messengers, Inflammatory Mediators, and Neuronal Plasticity in Cerebral Ischemia. In: Ito, U., Kirino, T., Kuroiwa, T., Klatzo, I. (eds) Maturation Phenomenon in Cerebral Ischemia II. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60546-8_3

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  • DOI: https://doi.org/10.1007/978-3-642-60546-8_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-61673-3

  • Online ISBN: 978-3-642-60546-8

  • eBook Packages: Springer Book Archive

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